Alzheimer’s disease. Picks disease.
AD is the commonest cause of dementia, accounting for almost half of cases. A clinico-pathologic entity comprising clinical evidence of dementia and histopathological evidence of neurofibrillary tangles and senile plaques in the brain.
Epidemiology
- Most common form of dementia, accounting for almost half of cases.
- Incidence- 123 per 100 000 population per year
- Prevalence- increases exponentially with age.
- Predominantly a disease of old age- the disorder rarely occurs under the age of 40 years, Before age 65, the prevalence, or proportion, of individuals with Alzheimer disease is less than 1%, but this rapidly increases to between 5% and 10% at age 65 years and to as high as 30% to 40% at age 85 and older.
- Gender M=F, women survive longer with the disease than men.
Etiology
- Genetic factors main etiological cause in 5% of all AD cases (hereditary AD); in families with early AD onset (between 40-60 years), the disease is transmitted mainly by autosomal dominant inheritance. Three genes responsible for early onset hereditary AD:
- Presenilin-1 gene on chromosome 14
- Presenilin-2 gene on chromosome 1
- Amyloid precursor protein gene on chromosome 21
- In sporadic AD form, disease is related to gene status of ApoE on chromosome 19
- Other risk factors are
- Gender (disease occurs more in women which may be due to their higher survivability)
- Education (more common in individuals of lower education status)
- Cranial traumas
- Smoking
- Depression etc.
Pathogenesis
- AD is characterised by neuronal loss and presence of amyloidal plaques and neurofibrillary tangles. These are not pathognomic to the disease as can be seen in other neurodegenerative conditions
- Amyloidal plaques are extracellular deposits that contain β-amyloid (Aβ) and other proteins, including presenilin 1, presenilin 2, α1 antichymotrypsin, apolipoprotein E, α2-macroglobulin, and ubiquitin.
- Plaques may also be found in cerebral and meningeal blood-vessel walls, producing cerebral amyloid angiopathy.
- Neurofibrillary tangles are intracellular deposits containing hyperphosphorylated tau (a microtubule-associated protein) and ubiquitin.
- It also typically shows diffuse cerebral atrophy with ventricular dilatation. Deficiency of acetylcholine in the hippocampus and in the cerebral neocortex, especially involving the basal forebrain cholinergic system, appears to be a key factor responsible for the profound memory loss in AD.
Clinical features
- Insidious onset.
- Clinical progression thought to comprise a presymptomatic phase of up to about 10 years characterized by the deposition of amyloid plaques, followed by a symptomatic phase of up to about 10 years, during which tangle formation occur